In recent years, evidence that sensitization of primary afferent nociceptors is an important event associated with chronic pain has been accumulating. The present study aimed to evaluate the participation of the prostaglandin and sympathetic components in the long-lasting sensitization of nociceptors induced by acute inflammation in mice. The intraplantar administration of carrageenan (100 μg) enhanced the nociceptive response to a small dose of PGE(2) (9 ng/paw) or dopamine (3 μg/paw) up to 30 days later. This long-lasting sensitization is dependent on dopaminergic and prostanoid systems, since the pre-treatment with chlorpromazine (3 μg/paw) or indomethacin (100 μg/paw), but not local (6 μg/paw) or systemic (6 mg/kg) treatment with morphine, prevented its development. In agreement with this idea, the previous intraplantar administration of hyperalgesic doses of PGE(2) or dopamine also induced long-lasting sensitization, which was fully prevented by pretreatment with EP(4) and D(1) antagonists, respectively. In summary, the present work described in mice a long-lasting sensitization of nociceptors, initiated by an acute inflammatory stimulation and dependent on dopaminergic and prostanoid systems. The present data represent new insights on the mechanisms of peripheral sensitization that could contribute to establish the basis of new therapeutic strategies for acute and chronic inflammatory pain.
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http://dx.doi.org/10.1016/j.pbb.2012.11.006 | DOI Listing |
Int Immunopharmacol
December 2024
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del IPN, Unidad Sede Sur, Calzada de los Tenorios No. 235, Col. Granjas Coapa, Tlalpan, CP 14330 Mexico City, Mexico; Centro de Investigación sobre el Envejecimiento, Centro de Investigación y de Estudios Avanzados del IPN, Unidad Sede Sur, Calzada de los Tenorios No. 235, Col. Granjas Coapa, Tlalpan, CP 14330 Mexico City, Mexico. Electronic address:
Mast cells (MC) are crucial effectors in immediate allergic reactions. Monomeric IgE sensitizes MC and triggers various signaling responses. FcεRI/IgE/antigen crosslinking induces the release of several mediators, including bioactive lipids, but little is known about endocannabinoids (eCBs) secretion.
View Article and Find Full Text PDFNPJ Vaccines
December 2024
Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
Eilat (EILV)/chikungunya virus (CHIKV), an insect-based chimeric alphavirus was previously reported to protect mice months after a single dose vaccination. The underlying mechanisms of host protection are not clearly defined. Here, we assessed the capacity of EILV/CHIKV to induce quick and durable protection in cynomolgus macaques.
View Article and Find Full Text PDFCell Rep
November 2024
Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address:
Stress can have profound consequences on mental health. While much is known about the neural circuits supporting associative memories of stressful events, our understanding of the circuits underlying the non-associative impacts of stress, such as heightened stress sensitivity and anxiety-related behavior, is limited. Here, we demonstrate that the ventral hippocampus (vHC) and basolateral amygdala (BLA) support distinct non-associative behavioral changes following stress.
View Article and Find Full Text PDFNeurobiol Pain
September 2024
Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
Persistent hyperactivity of nociceptors is known to contribute significantly to long-lasting sensitization and ongoing pain in many clinical conditions. It is often assumed that nociceptor hyperactivity is mainly driven by continuing stimulation from inflammatory mediators. We have tested an additional possibility: that persistent increases in excitability promoting hyperactivity can be induced by a prototypical cellular signaling pathway long known to induce late-phase long-term potentiation (LTP) of synapses in brain regions involved in memory formation.
View Article and Find Full Text PDFEur J Pain
September 2024
Department of Health Psychology, KU Leuven, Leuven, Belgium.
Background And Objectives: Central sensitization (CS) is believed to play a role in many chronic pain conditions. Direct non-invasive recording from single nociceptive neurons is not feasible in humans, complicating CS establishment. This review discusses how secondary hyperalgesia (SHA), considered a manifestation of CS, affects physiological measures in healthy individuals and if these measures could indicate CS.
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